HIF-1α, a novel piece in the NF-κB puzzle

TY - JOUR

T1 - HIF-1α, a novel piece in the NF-κB puzzle

AU - Bandarra, Daniel

AU - Rocha, Sonia

PY - 2015/4/28

Y1 - 2015/4/28

N2 - Hypoxia, or low oxygen availability, is an important physiological stimulus for multicellular organisms. Molecularly, hypoxia induces a transcriptional programme directed at restoration of oxygen homeostasis and cellular survival. Hypoxia and inflammation are intimately linked, and even though it is appreciated that NF-kB regulates the HIF system, little is known about how HIF regulates NF-kB. In a recent report we have shown that HIF-1α has an important role in regulating NF-kB. Importantly, HIF-1α acted to constrain NF-kB transcriptional activity, in mammalian cells and in the in vivo genetic model of Drosophila. Reduction of HIF-1α resulted in increased levels of specific NF-kB targets, by a mechanism dependent on TAK/IKK and CDK6 kinases. Deletion of the HIF-1α homologue in Drosophila, Sima, resulted in hypersensitivity to infection due to uncontrolled NF-kB. This report delineated for the first time the contribution of HIF-1α towards the NF-kB pathway, and demonstrated the importance of HIF-1α presence for the restraint of the inflammatory response in vivo. The importance of this crosstalk between HIF and NF-kB is significant, as it could create potential new therapies in diseases where hypoxia and inflammatory are prevalent.

AB - Hypoxia, or low oxygen availability, is an important physiological stimulus for multicellular organisms. Molecularly, hypoxia induces a transcriptional programme directed at restoration of oxygen homeostasis and cellular survival. Hypoxia and inflammation are intimately linked, and even though it is appreciated that NF-kB regulates the HIF system, little is known about how HIF regulates NF-kB. In a recent report we have shown that HIF-1α has an important role in regulating NF-kB. Importantly, HIF-1α acted to constrain NF-kB transcriptional activity, in mammalian cells and in the in vivo genetic model of Drosophila. Reduction of HIF-1α resulted in increased levels of specific NF-kB targets, by a mechanism dependent on TAK/IKK and CDK6 kinases. Deletion of the HIF-1α homologue in Drosophila, Sima, resulted in hypersensitivity to infection due to uncontrolled NF-kB. This report delineated for the first time the contribution of HIF-1α towards the NF-kB pathway, and demonstrated the importance of HIF-1α presence for the restraint of the inflammatory response in vivo. The importance of this crosstalk between HIF and NF-kB is significant, as it could create potential new therapies in diseases where hypoxia and inflammatory are prevalent.

U2 - 10.14800/ics.792

DO - 10.14800/ics.792

M3 - Article

VL - 2

JO - Inflammation and Cell Signaling

JF - Inflammation and Cell Signaling

IS - 1

M1 - e792

ER -